Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease that has the potential to cause serious morbidity and early mortality and is responsible for tremendous costs to affected individuals and society. A striking feature of SLE is variation in health outcomes. In particular, substantial research documents ethnic disparities in SLE risk and severity. In spite of the magnitude of variation in SLE health outcomes, and the potential importance for patients, physicians and society, many questions remain about the underlying causes. For example, it remains unclear whether ethnic disparities in SLE outcomes reflect primarily individual, social, environmental or genetic variation in risk or interactions among these factors. Our lack of understanding is at least partially due to the challenges of assembling a sufficiently large and diverse cohort of SLE patients, measuring the full range of potentially important risk factors, and accurately assessing health outcomes. The current proposal represents a unique combination of clinical and investigative resources that has been developed to address this critically important issue. Specifically, we will: 1) determine the relative contributions of demographic, socioeconomic, psychosocial, behavioral and genetic factors to health outcomes in SLE;and 2) characterize changes in health outcomes over time and the contribution of these explanatory factors to temporal changes in outcome. A primary focus of this project will be the relationship of ethnicity to SLE outcomes, and in particular understanding the roles of genetics and other factors (e.g., socioeconomic, psychosocial, etc.) as mediators of ethnic disparities in outcome. Our study population will be approximately 1,000 SLE patients enrolled in the Lupus Outcome Study. We will use validated instruments to assess the following outcomes: general health status, disease activity and cumulative damage. A unique feature of the current proposal is the depth and breadth of potentially important explanatory factors that will be considered. In addition to traditional risk factors, these include novel measures of community characteristics obtained through "geocoding" to small geographic areas and ancestry informative genetic markers. Due to the size and scope of this project, in conjunction with the rich resources and expertise of the MCRC, this project should substantially increase our understanding of health disparities in SLE and their underlying causes and guide efforts to remedy these disparities.